The homozygous M712T mutation of UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase results in reduced enzyme activities but not in altered overall cellular sialylation in hereditary inclusion body myopathy

Stephan Hinderlich, Ilan Salama, Iris Eisenberg, Tamara Potikha, Lars R. Mantey, Kevin J. Yarema, Rüdiger Horstkorte, Zohar Argov, Menachem Sadeh, Werner Reutter, Stella Mitrani-Rosenbaum

Research output: Contribution to journalArticlepeer-review

Abstract

Hereditary inclusion body myopathy (HIBM) is a neuromuscular disorder, caused by mutations in UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase, the key enzyme of sialic acid biosynthesis. In Middle Eastern patients a single homozygous mutation occurs, converting methionine-712 to threonine. Recombinant expression of the mutated enzyme revealed slightly reduced N-acetylmannosamine kinase activity, in agreement with the localization of the mutation within the kinase domain. B lymphoblastoid cell lines derived from patients expressing the mutated enzyme also display reduced UDP-N- acetylglucosamine 2-epimerase activity. Nevertheless, no reduced cellular sialylation was found in those cells by colorimetric assays and lectin analysis, indicating that HIBM is not directly caused by an altered overall expression of sialic acids.

Original languageEnglish
Pages (from-to)105-109
Number of pages5
JournalFEBS Letters
Volume566
Issue number1-3
DOIs
StatePublished - 21 May 2004
Externally publishedYes

Keywords

  • GNE
  • GNE, UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase
  • HIBM, hereditary inclusion body myopathy
  • Hereditary inclusion body myopathy
  • ManNAc kinase, N-acetylmannosamine kinase
  • UDP-GlcNAc 2-epimerase, UDP-N-acetylglucosamine 2-epimerase

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